Khullar Dinesh, Gupta Anish Kumar, Singh Kulwant
Department of Nephrology and Renal Transplant Medicine, Max Super Speciality Hospital Saket, New Delhi, India.
Card Fail Rev. 2024 Dec 23;10:e19. doi: 10.15420/cfr.2024.11. eCollection 2024.
Heart failure (HF) is a major contributor to hospitalisations and accounts for 7% of cardiovascular-related deaths, with patients who have chronic kidney disease and type 2 diabetes at heightened risk. Existing treatment guidelines inadequately address these comorbidities. Steroidal mineralocorticoid receptor antagonists (MRAs) are commonly used in HF with reduced ejection fraction but pose risks, such as hyperkalaemia and acute kidney injury. Finerenone, a non-steroidal MRA, offers a safer alternative, with higher selectivity, reduced electrolyte disturbances and beneficial effects on heart and kidney tissues. Preclinical studies show anti-inflammatory and anti-fibrotic effects, while phase III trials (ARTS and ARTS-HF) demonstrated fewer hyperkalaemia incidents compared with spironolactone. In phase III trials (FIDELIO-DKD and FIGARO-DKD), finerenone reduced HF hospitalisations by 22% in patients with chronic kidney disease and type 2 diabetes. The FINEARTS-HF trial found that finerenone significantly reduced the risk of worsening HF events or CV death in patients with HF with mildly reduced or preserved ejection fraction. Its combination with therapies, such as sodium-glucose cotransporter 2 inhibitors, shows promise and ongoing trials, such as REDEFINE-HF, FINALITY-HF and CONFIRMATION-HF, are investigating its efficacy in other HF phenotypes. These studies will further establish the role of finerenone in managing cardio-renal-metabolic diseases.
心力衰竭(HF)是导致住院的主要原因,占心血管相关死亡的7%,慢性肾病和2型糖尿病患者的风险更高。现有治疗指南对这些合并症的处理不够充分。甾体类盐皮质激素受体拮抗剂(MRAs)常用于射血分数降低的心力衰竭患者,但存在高钾血症和急性肾损伤等风险。非甾体类MRA非奈利酮提供了一种更安全的选择,具有更高的选择性,减少电解质紊乱,并对心脏和肾脏组织有有益作用。临床前研究显示出抗炎和抗纤维化作用,而III期试验(ARTS和ARTS-HF)表明,与螺内酯相比,高钾血症事件更少。在III期试验(FIDELIO-DKD和FIGARO-DKD)中,非奈利酮使慢性肾病和2型糖尿病患者的心力衰竭住院率降低了22%。FINEARTS-HF试验发现,非奈利酮显著降低了射血分数轻度降低或保留的心力衰竭患者发生心力衰竭事件恶化或心血管死亡的风险。它与钠-葡萄糖协同转运蛋白2抑制剂等疗法联合使用显示出前景,正在进行的试验,如REDEFINE-HF、FINALITY-HF和CONFIRMATION-HF,正在研究其在其他心力衰竭表型中的疗效。这些研究将进一步确立非奈利酮在管理心肾代谢疾病中的作用。